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Negative regulation of Ros receptor tyrosine kinase signaling: An epithelial function of the SH2 domain protein tyrosine phosphatase SHP-1

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Official URL:https://doi.org/10.1083/jcb.152.2.325
PubMed:View item in PubMed
Creators Name:Keilhack, H. and Mueller, M. and Boehmer, S.A. and Frank, C. and Weidner, K.M. and Birchmeier, W. and Ligensa, T. and Berndt, A. and Kosmehl, H. and Gunther, B. and Mueller, T. and Birchmeier, C. and Boehmer, F.D.
Journal Title:Journal of Cell Biology
Journal Abbreviation:J Cell Biol
Page Range:325-334
Date:22 January 2001
Keywords:Protein Tyrosine Phosphatase, Regulation, Receptor Tyrosine Kinase, Epididymis, Fertility, Animals, Mice
Abstract:Male "viable motheaten" (me(v)) mice, with a naturally occurring mutation in the gene of the SH2 domain protein tyrosine phosphatase SHP-1, are sterile. Known defects in sperm maturation in these mice correlate with an impaired differentiation of the epididymis, which has similarities to the phenotype of mice with a targeted inactivation of the Ros receptor tyrosine kinase. Ros and SHP-1 are coexpressed in epididymal epithelium, and elevated phosphorylation of Ros in the epididymis of me(v) mice suggests that Ros signaling is under control of SHP-1 in vivo. Phosphorylated Ros strongly and directly associates with SHP-1 in yeast two-hybrid, glutathione S-transferase pull-down, and coimmunoprecipitation experiments. Strong binding of SHP-1 to Ros is selective compared to six other receptor tyrosine kinases. The interaction is mediated by the SHP-1 NH(2)-terminal SH2 domain and Ros phosphotyrosine 2267. Overexpression of SHP-1 results in Ros dephosphorylation and effectively downregulates Ros-dependent proliferation and transformation. We propose that SHP-1 is an important downstream regulator of Ros signaling.
Publisher:Rockefeller University Press (U.S.A.)
Additional Information:Copyright (c) 2001 by The Rockefeller University Press
Item Type:Article

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